Project Summary/Abstract Social animals, including humans and rodents, have an inherent drive to seek out and create bonds with conspecifics that benefit their survival. This drive for social contact is diminished in multiple human psychiatric and neurological disorders, including autism spectrum disorders, schizophrenia, and depression. The underlying brain structures and circuits that mediate sociability, defined as the preference and desire for social interaction, are under intense investigation as researchers seek new targets for circuit-based interventions of these disorders. The hippocampus is a brain structure with crucial roles in memory and behavior. Appearing as an extended ?C?-shaped structure in rodents, the hippocampus can be further defined along its longitudinal (dorsoventral) axis. The dorsal (dHPC) and ventral (vHPC) hippocampus are proposed to have different functional roles, with dHPC regulating cognitive functions including spatial navigation and contextual memory, and vHPC influencing emotional processing and anxiety. Inhibition of vHPC increases sociability in rodents, likely due to decreased anxiety. Whether the hippocampus can influence sociability independently of anxiety remains unclear. The hippocampus can be additionally subdivided into the Cornu Ammonis subfields CA1-CA4 along its transverse axis. The hippocampal subregion CA2 has recently emerged as a crucial regulator of social recognition memory (SRM) and behavior. Global knockout of genes that, in the hippocampus, are exclusively expressed in CA2 results in decreased SRM, social aggression (SA), and sociability. In contrast, while acute or chronic inhibition of the dorsal region of CA2 (dCA2) reduce SRM and SA, it does not alter sociability. Given the importance of dCA2 in social memory and behavior, and the role of vHPC in emotional regulation, I hypothesize that ventral CA2 (vCA2) may regulate sociability. My preliminary results indicate that acute pharmacogenetic inhibition of vCA2 results in a significant reduction in sociability, without a concomitant change in anxiety. I will test my hypothesis of a role for vCA2 in sociability through two aims: first, I will probe the necessity and sufficiency of vCA2 in social- and non-social behaviors (Aim 1). I will then investigate the underlying vCA2 projections and activity that are important for vCA2?s role in social behavior (Aim 2). Together, these results will expand understanding of the brain circuits that underlie sociability, and potentially identify vCA2 as a new target for treatment of disorders with reduced social interest.